2023-07-05 アリゾナ大学
◆この研究により、モルヒネの慢性使用による副作用に注意が必要であり、オピオイド以外の代替療法の開発が重要であることが示唆されました。今後の研究で、オピオイドの作用メカニズムについてより詳細な理解が進むことが期待されます。
<関連情報>
- https://news.arizona.edu/story/study-shows-how-morphine-may-contribute-bone-loss-and-cancer-induced-bone-pain
- https://journals.lww.com/pain/Fulltext/9900/Morphine_induced_osteolysis_and_hypersensitivity.331.aspx
モルヒネによる骨溶解と知覚過敏は、toll様受容体-4を介することが、転移性乳がんのマウスモデルで明らかになった。 Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer
Thompson, Austen L.; Grenald, Shaness A.; Ciccone, Haley A.; Mohty, Dieter; Smith, Angela F.; Coleman, Deziree L.a; Bahramnejad, Erfana; De Leon, Erickb; Kasper-Conella, Loganb; Uhrlab, Jennifer L.c; Margolis, David S.; Salvemini, Daniela; Largent-Milnes, Tally M.; Vanderah, Todd W.
PAIN Published:June 15, 2023
DOI: 10.1097/j.pain.0000000000002953
Abstract
The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism.
